Daclatasvir (brand name Daklinza) is a new medication used to treat hepatitis C. It was
approved in Europe in August 2014 for treatment of adults with chronic
hepatitis C genotypes 1, 2, 3 or 4.
For some people, daclatasvir can be used in
interferon-free regimens with other oral hepatitis C medications. For others,
daclatasvir can shorten treatment when added to pegylated interferon and
ribavirin. Successful treatment reduces the risk of long-term complications of
hepatitis C such as liver cancer or needing a liver transplant.
How does
daclatasvir work?
Daclatasvir is one of the new direct-acting antiviral
drugs that target different steps of the hepatitis C virus (HCV) lifecycle. It
is the first-ever approved HCV NS5A replication complex inhibitor, meaning it
interferes with a protein the virus uses to reproduce.
Daclatasvir should be combined with other medications,
which may include other direct-acting antivirals that work differently – sofosbuvir (Sovaldi)
or the HCV protease inhibitor asunaprevir (Sunvepra)
– or pegylated interferon and ribavirin.
Who can
use daclatasvir?
Daclatasvir is indicated for use by adults with
chronic hepatitis C, meaning infection lasting more than six months. It is
approved for people with HCV genotype 1, 2, 3 or 4. Genotype 1 is the most
common type in Europe and considered the hardest to treat.
Daclatasvir can be used by people being treated for
hepatitis C for the first time (known as 'treatment-naive') and for retreatment
of people who were not cured with previous interferon-based therapy (known as
'treatment-experienced').
The safety and effectiveness of daclatasvir for people
with HIV and HCV co-infection has not yet been determined, but this is now
being tested. Studies have shown that daclatasvir does not have problematic
interactions with most widely used HIV drugs. People with HIV and HCV co-infection
who want to take daclatasvir should do so under the care of a doctor who has
experience treating both HIV and HCV.
Daclatasvir can be used by people with all stages of
compensated liver disease including cirrhosis. However, it works better for
people with less advanced liver damage. Daclatasvir is now being tested for
people with chronic hepatitis C who are awaiting or have received liver
transplants.
How is
daclatasvir taken?
Daclatasvir is available in 30 and 60mg tablets, and
the usual dose is 60mg once daily with or without food. It must be used in
combination with other hepatitis C medications and is not effective if taken
alone. Treatment should be managed by a doctor who has experience treating hepatitis
C.
| |
Combined
with:
|
Length
of treatment
|
|
Genotype
1
|
Daclatasvir & sofosbuvir
|
12 weeks (no cirrhosis)
24 weeks (with cirrhosis)
|
|
Genotype
1
|
Daclatasvir & sofosbuvir & ribavirin
|
12 weeks (post-liver transplant, no cirrhosis) 12 weeks (with cirrhosis A or B)
24 weeks (with decompensated cirrhosis)
|
|
Genotype
2
|
Daclatasvir & sofosbuvir
|
Evidence
lacking to make a recommendation on duration; at least 12 weeks.
|
|
Genotype 3
|
Daclatasvir & sofosbuvir
|
12 weeks (no cirrhosis)
|
|
Genotype
3
|
Daclatasvir & sofosbuvir & ribavirin
|
12 weeks (post-transplant, no cirrhosis) 24 weeks (with cirrhosis)
|
|
Genotype
4
|
Daclatasvir & sofosbuvir
|
12 weeks (no cirrhosis)
24 weeks (with cirrhosis)
|
|
Genotype
4
|
Daclatasvir & sofosbuvir & ribavirin
|
12 weeks (post-transplant or with cirrhosis A or B)
24 weeks (with decompensated cirrhosis)
|
Daclatasvir plus weekly pegylated interferon
injections and ribavirin pills for 24 weeks is another option for people with
genotype 4. Slow responders should continue on pegylated interferon and
ribavirin for 48 weeks.
How
effective is daclatasvir?
Daclatasvir
works better for some people than for others. Several factors predict how well
someone will respond, including HCV genotype, extent of liver damage and
previous treatment history. People with liver cirrhosis do not respond as well
as those with mild or moderate liver fibrosis. Depending on which drugs
daclatasvir is combined with, people who are new to treatment may have a better
chance of being cured than those with little or no response to prior treatment.
However,
factors that traditionally predict poor response to interferon-based therapy do
not make as much difference with interferon-free treatment. These factors may
be overcome by prolonging treatment or by adding another direct-acting
antiviral or ribavirin.
Daclatasvir
treatment response
People with sustained virological response (SVR), who
still have undetectable HCV viral load 12 weeks after finishing treatment
(known as 'SVR12'), are considered cured.
A phase 2 study (AI444040) looked at people with HCV
genotype 1, both previously untreated and those already treated with pegylated
interferon and ribavirin plus the older HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivo). Daclatasvir plus sofosbuvir
cured 100% of people in both groups treated for either 12 or 24 weeks.
Daclatasvir
plus sofosbuvir for 24 weeks was also tested in a smaller number of previously
untreated people with HCV genotype 2 or 3. Daclatasvir plus sofosbuvir alone
cured 96% of people with genotype 2 and 89% of those with genotype 3. Adding
ribavirin brought the cure rate for genotype 3 up to 100% as well.
In the COMMAND-4 trial (AI444042) daclatasvir
was tested in combination with pegylated interferon and ribavirin for
previously untreated people with HCV genotype 4. About 80% of
people with or without cirrhosis were cured with the triple combination – more
than twice as many as those taking interferon and ribavirin alone.
Daclatasvir's effectiveness in 'real world' use may be
somewhat lower than cure rates seen in clinical trials, in part because
patients may be sicker or have other conditions that make treatment more
complicated.
What are
the side effects of daclatasvir?
Daclatasvir is generally well tolerated with no known
specific side effects of its own. The most common side effects seen in people
taking daclatasvir with sofosbuvir are fatigue, nausea and headache.
Taking daclatasvir with interferon and ribavirin can lead
to additional side effects including fever, muscle and joint aches, itching,
depression, anaemia (low haemoglobin level) and neutropenia (low white blood
cell count). Ribavirin can also cause birth defects, so it should not be used
by pregnant women or their male partners.
Does daclatasvir interact with other drugs?
Daclatasvir
can interact with other drugs that are processed by the same enzymes in the
liver and intestines. These include some antibiotics, TB medications,
anti-seizure drugs and herbal products containing St John's wort. Sometimes
drug doses can be adjusted to overcome these interactions, but some medications
should not be used together with daclatasvir. Information about specific drug
interactions is available online at www.hep-druginteractions.org.
How can
I get daclatasvir?
Daclatasvir is available by prescription in several
European Union countries to treat genotype 1, 2, 3 and 4 hepatitis C. Ask your
GP or liver specialist if daclatasvir is available in your country and if it
may be a good option for you.
When to start treatment will depend on a number of
factors, including severity of liver damage (as determined by FibroScan or a liver biopsy). People
with mild liver disease may be able to wait, and more new hepatitis C
medications that can be used in interferon-free treatment are coming soon.
However, the decision to wait must take into account how fast your liver
disease might progress – which is hard to predict – and how
soon these new treatments will be approved in your country.
Factsheet reviewed April 2022.